ADHD May Have Genetic Component

Action Points

Explain to interested patients that children with attention-deficit hyperactivity disorder (ADHD) were more likely than other kids to have large chunks of deleted or duplicated DNA called copy number variants.

Note that this study suggests a genetic component to the disorder.

Children with attention-deficit hyperactivity disorder (ADHD) were more likely than other kids to have large chunks of deleted or duplicated DNA called copy number variants, possibly establishing a genetic component to the disorder, researchers found.

Although the majority of children with ADHD did not have these variants, the findings suggest that ADHD is not simply a behavioral disorder, but a neurodevelopmental one like autism, according to Anita Thapar, MD, of Cardiff University in Wales. She and her colleagues reported the results online in The Lancet.

"This is really exciting because it gives us the first direct genetic link to ADHD," Thapar said at a press conference.

Finding a genetic component may help take away the stigma of ADHD, which some people believe is not a real disorder or is the result of bad parenting, she said.

The study may also help contribute to the understanding of the biology of the brain, Thapar said.

"Through this, in the future, it's going to be the start of a much more scientific venture because our findings are going to help unravel the biological basis of ADHD," she said. "And that's going to be really important, in turn, ... to develop new and much more effective treatments for affected individuals."

"Of course, this won't happen immediately," she cautioned.

In an editorial accompanying the paper, J. Peter Burbach, PhD, of University Medical Center Utrecht in the Netherlands, also called the results exciting, but noted that they had unclear clinical significance.

"The first gains beyond today's study might be initial insights into the pathogenesis and neurobiology of brain development as influenced by these genetic variants," he wrote.

"This knowledge will eventually enter the clinic and might affect the way people think about and treat neurodevelopmental disorders by accounting for the biological consequence of the specific patient's genotype," Burbach added.

Despite a demonstrated high level of heritability, some people have continued to claim that ADHD is mainly a social construct, Thapar and her colleagues wrote in their paper.

So they decided to look for large, rare copy number variants -- which have been linked to other neurodevelopmental disorders -- in patients with ADHD.

They compared the genomes of 366 white ADHD patients ages 5 to 17 with 1,047 matched controls from the 1958 British Birth Cohort. Psychiatric data were not available for the control group.

All of the patients with ADHD met criteria for the disorder or for hyperkinetic disorder, but not for schizophrenia and autism.

The burden of large (greater than 500 kb) and rare (less than 1% population frequency) copy number variants was assessed using two arrays. The researchers included only those identified on both arrays to control for false-positives.

Overall, the burden of large, rare copy number variants among children with ADHD was more than double that among the controls (15.6% versus 7.5%, P=8.9x10-5).

The rate was particularly high (42.5%) among the 33 children with ADHD who also had an intellectual disability, defined as an IQ of less than 70, although those with higher IQ also had a significantly elevated rate compared with the controls (12.5%, P=0.0077).

So, even though the burden of copy number variants was greater in patients with ADHD, the majority of children did not have them.

There was a significant amount of overlap between the copy number variants identified in the patients with ADHD and areas of the chromosomes that have been implicated in both autism (P=0.0095) and schizophrenia (P=0.01).

The results suggest that there could be a shared biological basis to ADHD and autism, even though the two disorders have been thought of as entirely distinct entities, according to the researchers.

Only the schizophrenia finding, however, was validated in a separate cohort of patients and controls from Iceland.

The study was funded by Action Research, Baily Thomas Charitable Trust, Wellcome Trust, and the U.K. Medical Research Council. The study makes use of data generated by the Wellcome Trust Case-Control Consortium. The deCODE replication was supported by funding from the European Union.

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